The role of amino acid-induced mammalian target of rapamycin complex 1(mTORC1) signaling in insulin resistance

Mammalian target of rapamycin (mTOR) controls cell growth and metabolism in response to nutrients, energy, and growth factors. Recent findings have placed the lysosome at the core of mTOR complex 1 (mTORC1) regulation by amino acids. Two parallel pathways, Rag GTPase-Ragulator and Vps34-phospholipase D1 (PLD1), regulate mTOR activation on the lysosome. This review describes the recent advances in understanding amino acid-induced mTOR signaling with a particular focus on the role of mTOR in insulin resistance. The enzyme mTOR plays key roles in the regulation of mammalian cell metabolism and is implicated in nutrient-induced insulin resistance. mTOR (mammalian target of rapamycin) is part of an intricate network of proteins that pass signals from the outside of the cell to intracellular effectors. Mee-Sup Yoon and Cheol Soo Choi from the Gachon University in Korea reviewed the protein complexes mTOR participates in, in particular mTOR complex 1 (mTORC1) and how activation of this complex by amino acids leads to a reduction in insulin signaling. In rats high levels of amino acids have been linked to hyperactive mTORC1 and insulin resistance. A clear picture of all the proteins involved in the regulation of mTOR by amino acids will point to new candidates for therapy of type 2 diabetes.